Simplified Methylation Protocol Revised as of Today

Don't know about alternating, but I have learned by experimenting that Fred and Rich are both right, at least in my case. I tried all four forms. Cyano was the weakest, it helped a little but not enough to take regularly. But I take the other three forms daily, and that makes a huge difference, I need all three of the natural forms. Tried the ProHealth B12 Extreme combo tablet, but I can not set the dosages that way. The dose/ratio that works for me, and has been working for several months now, after I worked up gradually, is: 5,000mcg mB12, 1500mcg aB12, and 1250mcg hB12. Some days I take more mB12, but do not take more than 10,000mcg total B12. And this is probably effective because I am using the more effective brands Fred recommended for mB12 (Jarrow) and aB12 (Country Life), plus hB12 as Rich recommends, but for that I am using ProHealth's hB12 (their hydroxy B12 works well and is less expensive than the other brand). Since the aB12 has folic acid, I take that in the PM, several hours apart from methylfolate. This combination, along with supporting supplements, has restored my ability to work (part-time low-stress work at home, but still, that is a vast improvement). If I stop taking the B12, I only last about 12-24 hours before major symptoms start returning.

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Kurt,
Could you post a link to the hb-12 on Prohealth ? I can't seem to locate it on my own.

Thanks,
Drex
Never mind, I found it. It's the sublingual tabs, right ? It helps when I spell things correctly.

Folic acid blocks absorption of methylfolate, causing a folate deficiency. Freddd and Rich can explain better, but that's the gist of it. There is a thread devoted to that here somewhere. It's recent.

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Hi, drex, leela, and the group.

I wouldn't go so far as to say that folic acid blocks the absorption of methylfolate. It does compete with it for absorption in the gut by the proton-coupled folate transporter molecules.
We've also discussed the fact that folic acid competes with the thymidylate pathway for use of the DHFR enzyme, and also that folic acid requires two NADPH molecules to be chemically reduced to the useful forms of folate. PWCs may be low in NADPH.

In Freddd's case, folic acid appears to be more deleterious than in most other people in the population, and probably also more deleterious than in most PWCs. I think this depends on the particular genetic polymorphisms that a person has inherited from their parents.

In any case, one thing Freddd and I appear to agree on is that it is preferable not to take much folic acid if you are trying to lift a partial methylation cycle block with methylfolate. It's hard to avoid folic acid in the U.S. and some other countries, because it is added to food grains in order to decrease the incidence of neural tube birth defects, such as spina bifida. It has been successful in this to some extent.

I should also note that the protocol used by Dr. Alan Vinitsky in Maryland uses folic acid as the only folate form, and it apparently does help quite a few people. He gives it sublingually in large dosages, together with hydroxocobalamin. Not everyone is able to convert folic acid to the active folate forms very readily, though.

You're welcome. These test results indicate that you have glutathione depletion and a partial methylation cycle block and that therefore methylation treatment should be of help to you.
These results also indicate that your folate metabolism is not as depleted as in many other PWCs, but it still needs some support, and there will likely be higher demands on it when the methylation cycle begins to operate more normally. The low RBC folate indicates that the cell membranes are damaged, which is usual in ME/CFS because of the oxidative stress that is associated with glutathione depletion.

These test results do not tell us what form or forms of folate it would be best to take. Based on the biochemistry, methylfolate directly supports the methylation cycle, and therefore my opinion is that it should be included. Freddd will likely agree with this. I also believe that it would likely be helpful to include some folinic acid, to provide support for the synthesis of DNA and RNA until the methylation cycle is running faster and is converting methylfolate into tetrahydrofolate at a higher rate. Tetrahydrofolate is the "hub" of the folate metabolism, and other folate forms can be made from it. Since yours is currently low, some folinic would probably help. Freddd will likely not agree with this, based on his personal experience, but I think this depends on each person's genetic polymorphisms. Unfortunately, we don't have data on these, or even have complete information on which ones are the important ones.

Best regards,

Rich

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Hi Rich,

I actually have no idea what percentage of people here at this forum have a difficulty with folic or folinic acid, and nobody does. However, there is no need to operate on theory on this any longer. Each person can pragmatically test it for themselves since Metafolin is easily available.

Based on a competition hypothesis, it might affect 100% of people, competing with natural folate forms from foods.

For those who depend on folinic/folic acid perhaps as many as 100% could find it insufficient as there is a maximum amount convertible per day for those who can.

30% may find it drastically insufficient because of impaired conversion capability.

20% will find it completely useless because of no ability to convert it.

What we don't know is what percentage will actually have paradoxical folate deficiency becasue of folic acid and/or folinic acid?

Metafolin has been on my list as a critical cofactor because it makes the whole thing "come alive" for quite a few people, and that could be 50% or better. I was in that group too. Now I know that the folic/folinic acid was actually causing deficiency and actually blocking the Metafolin could only be found out by trying the Metafolin.

You wondered, and so did I why I needed 8800mcg a day and now we may know, because most of it was wasted competing with folic/folinic acid. In another few months I will know how much Metafolin I need in the absence of folic/folinic acid.

Now we know what some of the symptoms are that indicate such paradoxical folate deficiencies; stomach and intestinal problems, especially those that come and go for unknown reasons or just stay or get worse; intermittent diarrhea/IBS, increased inflammation, increased allergic response, common "detox" symptoms triggered by folinic/folic-acid or glutathione, angular cheilitis, acne type lesions, other types of tissue generation/deterioration problems, depression, worsened neurological symptoms, personality changes, energy changes and some others. This is all rapidly and easily tested by each individual doing some A-B testing with Metafolin and folic or folinic acid. If they come and go with a few days lag time when switching back and forth it's a bingo. If the effects of Metafolin are very different from the effects of folinic or folic acid it's a bingo. If there are no differences then a person can use whatever form they wish without causing themselves problems. They can know quite definitively for themselves. They don't have to count an anybody's theories.

I also believe that it would likely be helpful to include some folinic acid, to provide support for the synthesis of DNA and RNA until the methylation cycle is running faster and is converting methylfolate into tetrahydrofolate at a higher rate. Tetrahydrofolate is the "hub" of the folate metabolism, and other folate forms can be made from it. Since yours is currently low, some folinic would probably help. Freddd will likely not agree with this, based on his personal experience

This is an individually testable hypothesis, do an A-B-C trial with Folinic acid, folinic acid plus Metafolin and Metafolin alone. I made that test because I found your hypothesis convincing. I also found my results convincing; folinic acid can cause paradoxical folate deficiency in at least some people. I am now in the C portion of my own A-B-C trials, Metafolin alone removing folic acid of all sources. I'm finding out how much difference folic acid made with Metafolin even with careful timing so that I didn't have methylation shutdown.

Even with my amazing response to mb12 I was unable to convince any of my doctors to prescribe Metanx or Deplin for off label usage so I had to wait until OTC Metafolin became available. I have had a lot of ill health and delays in healing because of the doctor's working theories concerning b12 and folic acid.

In this real life game of YOU BET YOUR LIFE don't count on theories. Test this yourself. And again, the response in this fast. Decades of symptoms can start receding in days.

Fredd, please excuse the sieve-brain, but did you mention yet, during this no-folic/folinic acid trial what you are using for aB12, since your previous recommended Country Life brand contains folic acid as well? Did you find a pure aB12 that is potent and useful? I am presuming here that you are not taking *just* Metafolin, but are taking in conjunction with both the forms of B12 you usually recommend.

I wouldn't go so far as to say that folic acid blocks the absorption of methylfolate. It does compete with it for absorption in the gut by the proton-coupled folate transporter molecules.
We've also discussed the fact that folic acid competes with the thymidylate pathway for use of the DHFR enzyme, and also that folic acid requires two NADPH molecules to be chemically reduced to the useful forms of folate. PWCs may be low in NADPH.

In Freddd's case, folic acid appears to be more deleterious than in most other people in the population, and probably also more deleterious than in most PWCs. I think this depends on the particular genetic polymorphisms that a person has inherited from their parents.

In any case, one thing Freddd and I appear to agree on is that it is preferable not to take much folic acid if you are trying to lift a partial methylation cycle block with methylfolate. It's hard to avoid folic acid in the U.S. and some other countries, because it is added to food grains in order to decrease the incidence of neural tube birth defects, such as spina bifida. It has been successful in this to some extent.

I should also note that the protocol used by Dr. Alan Vinitsky in Maryland uses folic acid as the only folate form, and it apparently does help quite a few people. He gives it sublingually in large dosages, together with hydroxocobalamin. Not everyone is able to convert folic acid to the active folate forms very readily, though.

Best regards,

Rich

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Hi Rich,

In Freddd's case, folic acid appears to be more deleterious than in most other people in the population, andprobably also more deleterious than in most PWCs.I think this depends on the particular genetic polymorphisms that a person has inherited from their parents.

So the 20% or 30% or 40% that suffer from this should be write offs just because "most" don't? I got very tired of having the "solutions" presented to me by doctors not only not working for me but making me worse. 50% of the total population has polymorphisms affecting the handling of folic acid. Folinic acid isn't that researched.

t's hard to avoid folic acid in the U.S. and some other countries, because it is added to food grains in order to decrease the incidence of neural tube birth defects, such as spina bifida. It has been successful in this to some extent.

Yes, folic acid added to white flour has been partially successful, 27% reduction in neural tube defects. So that means 73% were either made worse or no difference at all. How many of those neural tube defects were caused by the folic acid? Nobody knows because that question isn't being asked. It sounds like MOST didn't have the desired beneficial effect. The reports I read on this stated that only a 27% reduction was "disappointing". Something like twice that was expected. Why did the results miss the expectations by so much? Maybe because "MOST" don't have the expected pragmatic level of benefits the research had lead those calling for folic acid fortification to believe that it did. Again, lives and health destroyed by a belief in a faulty theory. So many studies concerning neurological diseases using cyanocbl/folic-acid/b6 as a usual trio are failures at proving to be a benefit. Also so many studies of multivitamins including the same trio, folic acid, cyanocbl and b6 proving to be a total failure in looking for benefit. Why do they keep beating the dead horses of cyanocbl and folic acid?

On this anybody who cares to can now test the hypothesis concerning folic and folinic acid for themselves. They don't have to believe anybody but their own experiences. They need to pay attention and distinguish startup from worsened or continuing. And maybe they find benefit in it for a short time until methylation is started. Of course that might only be 4 hours with Metafolin and methylb12. Mine stops within 2 hours of folic acid without Metafolin and restarts with my next dose after about 8 hours without folic acid. Mine has always been an ify kind of thing because of the folic acid. It's going to be a whole new experience for me to have functional cell formation 24/7.

Fredd, please excuse the sieve-brain, but did you mention yet, during this no-folic/folinic acid trial what you are using for aB12, since your previous recommended Country Life brand contains folic acid as well? Did you find a pure aB12 that is potent and useful? I am presuming here that you are not taking *just* Metafolin, but are taking in conjunction with both the forms of B12 you usually recommend.

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Hi Leela,

I happen to have about 9+ grams of adb12 crystal in my freezer that I use as a control. I did an injection series with some a year ago and found out that it was, as regards adb12 no different than the Country Life, and that it broke down in 10 days in solution even in the dark. It made methlb12 look outright stable. At that time I was not in paradoxical folate deficiency and was only taking the Country Life Dibencozide as 18mg about once a week. I am going to give it a try probably tonight after it gets dark and I can control the light in the kitchen now that I am reminded of it.

I find I have to go a month without adb12 to reliably be able to notice it when I take it. Weekly appears able to maintain equilibrium, for me anyway. I take mb12 3x per day and Metafolin 5x per day but am starting to cut back quantity now that I have eliminated folic acid. I am still going to test the Source Natural Dibencozide and I have something to compare it to.

Thank you, Kurt, this is so useful on so many counts. Could you remind me why it is important to take the folic acid away from the methylfolate?
ps THis is great news that the protocol has made such an improvement! How long have you been doing it? Do you think we will have to do it forever in order to maintain any functionality gains?

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Taking them separate seems to help the methylfolate work better. I've taken them together, but per Fred's suggestion tried them apart and noticed the improved effect. As Rich says, they probably compete for resources, but regardless, I can tell the difference. Methylfolate separate from folic acid seems to have a stronger effect.

I do think that until we find the 'rest of the story' on the full cause and solution to CFS the gains from the multi-B12 protocol (With the supporting nutrients) will require continued supplementation, just based on my experience and the reports of others. But that is a small price to pay to have a part of your life back. And one important benefit in my case (and also others on this protocol) is that other treatments are better tolerated and more effective.

Kurt,
Could you post a link to the hb-12 on Prohealth ? I can't seem to locate it on my own.
Thanks,
Drex
Never mind, I found it. It's the sublingual tabs, right ? It helps when I spell things correctly.

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Yes, the sublingual hB12 by ProHealth. You need a sharp knife to cut the tablets into quarters, anyway that is what I am doing and that works.

Don't know about alternating, but I have learned by experimenting that Fred and Rich are both right, at least in my case. I tried all four forms. Cyano was the weakest, it helped a little but not enough to take regularly. But I take the other three forms daily, and that makes a huge difference, I need all three of the natural forms. Tried the ProHealth B12 Extreme combo tablet, but I can not set the dosages that way. The dose/ratio that works for me, and has been working for several months now, after I worked up gradually, is: 5,000mcg mB12, 1500mcg aB12, and 1250mcg hB12. Some days I take more mB12, but do not take more than 10,000mcg total B12. And this is probably effective because I am using the more effective brands Fred recommended for mB12 (Jarrow) and aB12 (Country Life), plus hB12 as Rich recommends, but for that I am using ProHealth's hB12 (their hydroxy B12 works well and is less expensive than the other brand). Since the aB12 has folic acid, I take that in the PM, several hours apart from methylfolate. This combination, along with supporting supplements, has restored my ability to work (part-time low-stress work at home, but still, that is a vast improvement). If I stop taking the B12, I only last about 12-24 hours before major symptoms start returning.

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Kurt, how much methylfolate , (Metafolin?), do you take?

Really glad to hear you're doing better. What symptoms have resolved most for you?

I know Freddd has mentioned he reacts really badly to glutathione supplementation, but the TD form I have is the one thing that makes me feel better within an hour when I feel really toxic and awful.

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Like you, Leela, I need my NAC to help me manage my exposures to toxins. Having MCS in addition to CFS, I have to have regular liver assistance, and the NAC works for me on that level. I look forward to trying out your TD glutathione when I can afford it.

Don't know about alternating, but I have learned by experimenting that Fred and Rich are both right, at least in my case. I tried all four forms. Cyano was the weakest, it helped a little but not enough to take regularly. But I take the other three forms daily, and that makes a huge difference, I need all three of the natural forms. Tried the ProHealth B12 Extreme combo tablet, but I can not set the dosages that way. The dose/ratio that works for me, and has been working for several months now, after I worked up gradually, is: 5,000mcg mB12, 1500mcg aB12, and 1250mcg hB12. Some days I take more mB12, but do not take more than 10,000mcg total B12. And this is probably effective because I am using the more effective brands Fred recommended for mB12 (Jarrow) and aB12 (Country Life), plus hB12 as Rich recommends, but for that I am using ProHealth's hB12 (their hydroxy B12 works well and is less expensive than the other brand). Since the aB12 has folic acid, I take that in the PM, several hours apart from methylfolate. This combination, along with supporting supplements, has restored my ability to work (part-time low-stress work at home, but still, that is a vast improvement). If I stop taking the B12, I only last about 12-24 hours before major symptoms start returning.

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I want to respond to both Leela and Kurt in one swoop here.

I have found that I have such *EXTREME* reactions to the methyl B12, that I can't consider taking it any more. Even 250 mcg (a quarter tablet of the 1000 mcg Jarrow formula) can trigger a week long detox, (which I've verified in fecal metal tests), and which then throws me into a tailspin and demolishes the bit of fragile energy I have. The adB12 has also been challenging, but a bit more manageable. The cyanoB12 is the one I have taken regularly for many years, and never had any problems with, so I continue to do that one. The hB12 has not been problematic either, in the ltd doses that I've used. So that's the only one I intend to add to my routine for the time being.

I think that because we are all biochemically unique, we all have to find just the right combination of B12's and co-factors. I appreciate Kurt spelling his out so thoroughly. It confirms for me just how much of an experiment this methylation protocol really is. FLEXIBILITY and a willingness to adjust and readjust it, in order to find just the right forms, doses, and brands of B12 seem to be as much a part of the agenda as the B12's themselves. I look forward to hearing more input from others as they do their own B12 investigations.

Kurt, how much methylfolate , (Metafolin?), do you take?
Really glad to hear you're doing better. What symptoms have resolved most for you?

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I am doing well with 200mcg of methylfolate (yes, I am using Solgar Metafolin). Initially I could only tolerate 100mcg, and eventually may try a higher dose. However, the methylfolate really can hit me hard, overload my detox pathways, I have to be careful with that one.

As for symptoms, they are all improved somewhat, maybe 20% overall gain so far. That actually seems stable but there are still good days and bad days. There were some new sensations, some new B12 deficiency type pains for awhile, I attribute that to the reversal of B12 neuropathy and believe B12 deficiency hides some of the symptoms of B12 deficiency because it causes some neuropathy. When you start taking B12, particularly mB12, the nerves immediately start sending you sensations you have been missing before, and that is not always pleasant, but over time as the deficiency reverses those pains have subsided.

I agree. This is a great thread, and I'm learning a lot. THANK YOU to all who are contributing.
Like you, Leela, I need my NAC to help me manage my exposures to toxins. Having MCS in addition to CFS, I have to have regular liver assistance, and the NAC works for me on that level. I look forward to trying out your TD glutathione when I can afford it.
I want to respond to both Leela and Kurt in one swoop here.
I have found that I have such *EXTREME* reactions to the methyl B12, that I can't consider taking it any more. Even 250 mcg (a quarter tablet of the 1000 mcg Jarrow formula) can trigger a week long detox, (which I've verified in fecal metal tests), and which then throws me into a tailspin and demolishes the bit of fragile energy I have. The adB12 has also been challenging, but a bit more manageable. The cyanoB12 is the one I have taken regularly for many years, and never had any problems with, so I continue to do that one. The hB12 has not been problematic either, in the ltd doses that I've used. So that's the only one I intend to add to my routine for the time being.
I think that because we are all biochemically unique, we all have to find just the right combination of B12's and co-factors. I appreciate Kurt spelling his out so thoroughly. It confirms for me just how much of an experiment this methylation protocol really is. FLEXIBILITY and a willingness to adjust and readjust it, in order to find just the right forms, doses, and brands of B12 seem to be as much a part of the agenda as the B12's themselves. I look forward to hearing more input from others as they do their own B12 investigations.

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Just want to second what Dreambirdie says here. A common mistake I see made on these forums is patients over-generalizing their personal results to all other CFS patients. We are most definitely all different genetically, and our stage of illness and pathogen and toxin loads are unique. However we are all biochemically very similar, so there certainly are going to be common areas. But I agree, this is experimental, and we should be sensitive to our responses. That said, we also can often benefit by analyzing what happens when we react to something, where possible.

Dreambirdie, Here are some thoughts on what you reported. Since you have MCS, and respond so strongly to methyl B12, I would look into the possibility you are an 'overmethylator,' I have read that is common in MCS patients. However, you might just be so sensitive that forcing any major detox creates a problem. Since you know it is metals in your case, maybe a metals binder must be taken with any mB12? I know in my case I also had a very strong reaction to the initial 250 mcg doses I tried, not as bad as what you described, but enough that I did some research and decided I was probably deficient in magnesium and B6, so I added those co-factors in specific forms that I knew were better absorbed (mag chloride) and better tolerated (regular B6, not p5p), and also added Ester-C, and I was gradually able to tolerate mB12. In fact, over a few weeks something cleared out or re-started and I found I was able to tolerate more and more, up to my current dosing. But there was some experimentation to figure this all out, I have been working on this protocol since last summer, and it is fairly stable now. In fact the multi-B12 protocol is stable enough I am mostly leaving this alone right now, just continuing with what works, and adding other new CFS protocols, which are now working better than ever before. Anyway, in your situation I would not give up on mB12 since this is an important part of normal biochemistry, but would try to work out why this happened. And research what co-factors might be depleted in you personally that could create this response, and take an even smaller dose, maybe as small as you can manage (you can probably dissolve the tablets and take a few drops a day at first).

I have come across a major problem with taking ANY of the sublingual B12s. The one's recommended by Fred all contain either Sorbitol or Xylitol and both of these give me horrendous migraines that are unbearable. I know that Aspartame does this to me too and this is how I have come to the conclusion its these artificial sweetners I cannot tolerate.

I have found I am ok for 3 days and then they start getting worse and worse each day until I go for Acupucture to bring it to an end and of course stop the B12s. I am able to continue with the Carnitine Fumerate and 1/2 tab B Rights plus I get some of the B12 and active folates in the 3 Thorne Multi called Basic Nutrients I have been taking since 2007.

Its so disappointing because I noticed a very big difference in my energy when taking all the supplements especally the AdnB12.

I guess its unlikely that the B12s on their own could cause horrendous daily migraines?

I have come across a major problem with taking ANY of the sublingual B12s. The one's recommended by Fred all contain either Sorbitol or Xylitol and both of these give me horrendous migraines that are unbearable. I know that Aspartame does this to me too and this is how I have come to the conclusion its these artificial sweetners I cannot tolerate.

I have found I am ok for 3 days and then they start getting worse and worse each day until I go for Acupucture to bring it to an end and of course stop the B12s. I am able to continue with the Carnitine Fumerate and 1/2 tab B Rights plus I get some of the B12 and active folates in the 3 Thorne Multi called Basic Nutrients I have been taking since 2007.

Its so disappointing because I noticed a very big difference in my energy when taking all the supplements especally the AdnB12.

I guess its unlikely that the B12s on their own could cause horrendous daily migraines?

Pam

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Pam I would have thought it is far more likely to be the B12 causing this rather than the Sorbitol/Xylitol.

I have come across a major problem with taking ANY of the sublingual B12s. The one's recommended by Fred all contain either Sorbitol or Xylitol and both of these give me horrendous migraines that are unbearable. I know that Aspartame does this to me too and this is how I have come to the conclusion its these artificial sweetners I cannot tolerate.

I have found I am ok for 3 days and then they start getting worse and worse each day until I go for Acupucture to bring it to an end and of course stop the B12s. I am able to continue with the Carnitine Fumerate and 1/2 tab B Rights plus I get some of the B12 and active folates in the 3 Thorne Multi called Basic Nutrients I have been taking since 2007.

Its so disappointing because I noticed a very big difference in my energy when taking all the supplements especally the AdnB12.

I guess its unlikely that the B12s on their own could cause horrendous daily migraines?

Pam

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Hi Pam,

Sorbitol or Xylitol and both of these give me horrendous migraines that are unbearable

Sorbitol is a sugar alcohol that occurs naturally in such foods as apples and prunes

So the question is do plums, pears, peaches, raspberries, apples, mushrooms, oats and corn give you killer headaches? Plums (prunes), containing both sorbitol and xylitol ought to be a double whammy. A single bite of many fruits contains a lot more sweet alcohol than any of those tablets.
I guess its unlikely that the B12s on their own could cause horrendous daily migraines?

I'm not entirely sure of that. Let's consider the circumstances under which it could.

I have way too much experience with headaches. From about 1985 to 1995 I had chronic daily headaches and each two weeks like a clockwork, 3-5 day killer headaches. From 1989 when I was in a phase III Stadol study until 1995 I kept track of each headache, their characteristics and differences, all medications used and what if anything would abort them. I had them all in Supercalc 5 (spreadsheet like excel) and they made some very interesting graphs which allowed me to solve the problem of how to end them quickly after I succeeded in doing so 3 times in 7 years. Then a permanent end was put to them between May 21, 2003 and about 2 years later by removing the cause. While in referring to them many people called them "migraines" they were not actually migraines.

http://en.wikipedia.org/wiki/Migraine
The typical migraine headache is unilateral pain (affecting one half of the head) and pulsating in nature and lasting from 4 to 72 hours; symptoms include nausea, vomiting, photophobia (increased sensitivity to light), phonophobia (increased sensitivity to sound); the symptoms are generally aggravated by routine activity.[3][4] Approximately one-third of people who suffer from migraine headaches perceive an auraunusual visual, olfactory, or other sensory experiences that are a sign that the migraine will soon occur.[5]

And the article has a lot of other things about migraines.

I had a damaged neck and demyelinated areas in my neck. When a certain movement that would send shocks and icepick pains down my body I would also get an instantaneous severe headache in about 1/4 second.

I had inflamed veins in my scalp. Every muscle in my neck and head was tight and so painful that a light touch would put me through the roof. My neck was forced into a reverse of the normal curvature.

When any of these pains intensified by the muscles going into a big spasm or whatever I would feel it as a headache. Just as earphones can give the illusion of sound in the middle of your head, pains in the "helmet" of muscles and veins around the head can "stereo locate" as a headache inside your head.

Right now, Botox is sometimes used to relax these muscles in the neck and head that trigger terrible headaches. If a person has used botox for that, each dose of at least methylb12 will neutralize the Botox for about a day allowing the headache to return very rapidly.

The inflamed veins, inflamed endothelial tissues, can be caused by faulty tissue generation caused by lack of mb12 and/or methylfolate.

The tight tender muscles can be caused by neurological problems with mb12,adb12 and methylfolate deficiencies at the causes, as there are about 10 separate types of pains and causes of these pains involving these muscles. So if the neurological cause is still present and you feed the muscle adb12 suddenly it can make stronger contractions and trigger terrible headaches. Likewise if the neurological problems heal but the adb12 is still missing, the same "exhausted contraction" continues with severe pain and headaches. It took about two years of the active mb12 and adb12 with cofactors for all my muscles to be able to heal and repair and grow to sufficient capacity that the pains went away. The reverse curvature forced by tight muscles is a hallmark symptom of M.E.
The tightness and pain in the muscles are a combination of things so no one thing fixes it. With my doc I learned how to abort the headaches after 7 years. It required a combination of Valium and any of several pain meds like oxycodone, morphine or Stadol taken early in the headache and then a mini taper with diminishing doses each 2.5 hours to to keep it from coming back. 3 hours between and it would be back.

Mb12 can cause these headaches to kick up since the intensity of nerve signal increases and the nerves and muscles are still damaged resulting in terrible headaches. The headaches can also be caused when a person who has a very low level of accommodation to benzos hits about the 5th serum halflife period without taking at least a little which is why benzos have to be tapered to very low levels, they cause all sorts of rebound problems. At high accommodation levels improper withdrawal from benzos can cause seizures.

I think a good place to start is changing to a different B-complex without any folic acid at all. The best I've found (from the listed ingredient list) so far is the Douglas Labs.

Your energy response is very indicative of just how much you need the adb12. Source Natural makes a dibencozide sublingual of unknown effectiveness right now. I am going to test them but I have to wait long enough that I would be able to feel it. Somebody else has suggested the Dibol brand oral capsule as being effective for them. As my testing cycle with adb12 is about a month between brands it will take a while for me to test them. You could try it and see if either brand works for you by producing the energy.

I just want to add that after 4 days of no folic acid I am feeling better each day.